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Pharmaceuti cal Sector

Environmental

Report

May, 2002

Prepared by:

CP PCleaner Production Program

Environmental Report


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May, 2002

Prepared by:Cleaner Production Program - CPP

703, 7th Floor, Progressive Plaza, Beaumont Road, Civil Lines, Karachi.Tel #: +92-21-565 5835, 565 5836 Fax #: +92-21-565 5737

Email: [email protected], URL: http://www.cpp.org.pk


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Table of Content

Preface vi

Executive Summary vii

1Introduction

1.1 Background 11.2 Overview of the Pharmaceutical Sector Environmental Report 21.3 Pharmaceutical Sector of Pakistan

2

2Production Process

2.1 Raw Materials and Products 52.1.1 Products 52.1.2 Raw Materials 5

2.2 Main Production Facilities5

2.2.1 Storage Facilities 52.2.2 Manufacturing Facilities

6

2.2.3 Over Printing Area

62.2.4 Packaging Area7

2.3 Allied Facilities7

2.3.1 Quality Control (QC/QA) Laboratory 72.3.2 Ventilation Systems 72.3.3 Chillers and Cooling Towers 72.3.4 Fire Detection and Fighting Systems 7

2.3.5 Boilers 72.3.6 Water Softening Units 8

2.3.7 Water De-ionizing Units 82.3.8 Water Distillation Unit 82.3.9 Generators 82.3.10 Hydraulic Press 82.3.11 Shredder 82.3.12 Incinerator 8

2.4 Typical Production Processes 92.4.1 Dispensing 9


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Table of Content Pharmaceutical Sector Report

Cleaner Production Program (CPP) Page # ii

2.4.2 Tablets Manufacturing 92.4.3 Encapsulation 102.4.4 Syrups manufacturing 102.4.5 Manufacturing of Oral Powders for Suspensions 10 2.4.6 Creams, Ointments

and Lotions Manufacturing 10

2.4.7

Ijectibles Manufacturing11

2.4.8 Capsul Manufacturing Process11

Cleaner Producti on Program (CPP) Page # i

2.5 Utilities12

2.5.1 Water 122.5.2 Electricity 122.5.3 Fuels 13

3Environmental Issues and Impacts

3.1 Wastewater Pollution 143.1.1 General 143.1.2 Wastewater Sources and Quality 14

3.1.3 Wastewater Quantities 163.1.4 Wastewater Characteristics 163.1.5 Impacts Associated with Wastewater 173.1.6 Disposal of Wastewater 18

3.2 Air Emissions 193.2.1 Major Sources, Process and Qualitative Characteristics of Air Emission 193.2.2 Existing Situation on Point Emissions 203.2.3 Existing Situation on Diffused Emissions 213.2.4 Impacts of Air Pollutants on Environment and Human Health & Life 21

3.3 Process Solid Waste and Waste Chemicals23

3.3.1 Contaminated Process Solid waste and Waste Chemicals 23

3.3.2 Existing Disposal Practices of Contaminated Solid Waste 243.3.3 Non-Contaminated Process Solid Waste 25

3.4 Noise Pollution25

3.4.1 Noise Sources and Levels 253.4.2 Potential Impacts of Noise Pollution 26

4Recommendations


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Cleaner Production Program (CPP) Page # iii

4.1 Wastewater Treatment 274.1.1 General 274.1.2 Wastewater Quantities 274.1.3 Wastewater Characteristics and Effluent Quality Standards 27

4.1.4 Proposed Wastewater Treatment system for Removal ofOrganic Pollutants 284.1.5 Activated Carbon Adsorption Treatment for Removal of Phenols 31

4.2 Occupational Air Quality Control31

4.2.1 Enclosure of the Emission Sources 324.2.2 Criteria for Local or Spot Ventilation System 324.2.3 Criteria for General Area or Room Ventilation System 344.2.4 Monitoring 354.2.5 Exhaust or Re-circulating Air Carrying Particulate Matter from Granule &

powdered Ingredients Processes 35

4.3 Contaminated Solid Waste and Waste Chemicals and Management 354.3.1 Waste Segregation and Quantification 354.3.2 Prevention of Waste Generation 364.3.3 Storage of Contaminated Waste and Waste Chemicals 364.3.4 Contaminated Waste Treatment and Disposal by Incineration 364.3.5 Contaminated Glassware 384.3.6 Contaminated Emptied Drums 38

4.5 Occupational Health and Safety (OHS) Measures 38

4.5.1 Material Safety Data Sheets (MSDS) for Hazardous Substances

394.5.2 Fire Fighting System 39 4.5.3 Personal Protection Equipment (PPE)

40

4.5.4 First Aid Medical Treatment 404.5.5 Uniforms

40

4.5.6 Training and Procedures40

4.5.7 Records and Evaluation 41

4.6 Recommended Institutional Measures 41

4.6.1 Defining and Setting Objective and Policies 41

4.6.2 Areas of Responsibilities of EHS Department 414.6.3 Functions of EHS Department 42

AnnexureAnnexure-I: Main Features of an Air Handling System


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Cleaner Production Program (CPP) Page # iv

List of Tables

Table 1.1: Province wise distribution of Pharmaceutical IndustriesTable 1.2: Annual Sales of Top Ten Products Rs. m From January 2001 to December2001

Table 1.3: Sales of Leading Companies

Table 3.1: Typical Wastewater Generation Sources and Qualitative CharacteristicsPharmaceutical Plant

Table 3.2: Composite Process Wastewater Characteristics

Table 3.3: Environmental Impacts of Wastewater

Table 3.4: Air Emission Sources/Operations and Major Pollutants

Table 3.5: Impacts of Air Pollutants on Environment and Human Health & Life

Table 3.6: Contaminated process Solid Waste and Waste Chemicals Pharmaceutical

Formulation Industry

Table 3.7: Non-Contaminated Process Solid Waste Pharmaceutical Formulation Industry

Table 3.8: Typical Noise Levels in Pharmaceutical Industry

Table 4.1: Maximum Day Composite Wastewater Characteristics and RequiredDegree of Treatment Pharmaceutical Formulation Plant

Table 4.2: Treatment Efficiencies Based on Composite WastewaterCharacteristics Existing Extended Aeration Activated Sludge Plant(Pharmaceutical Formulation Plant)

Table 4.3: Range of Capture velocities for Dusts, Vapors, and Fumes


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Cleaner Production Program (CPP) Page # v

List of Figures

Figure 4.1: Wastewater Treatment Plant

Figure 4.2: Rotary Kiln


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Cleaner Production Program (CPP) vi

Preface

This report is compiled by the Cleaner Production Program (CPP). The main objective ofCPP is to continue the dissemination of environmental and cleaner production solutions andenabling the industrial units at the sector level to implement the same in a cost effectivemanner.

This report is a step towards the dissemination of information about the environmentalproblems of Pharmaceutical Sector. It also recommends possible cleaner productionsolutions and estimated required investments to mitigate these problems in order to complywith the present and future environmental legislation in Pakistan.

It is anticipated that this report will help Pharmaceutical Industries to initiate efforts tocombat the environmental problems and produce cleaner pr oducts.

This report on the Pharmaceutical Sector has been prepared on the basis of informationcollected from various pharmaceutical units, different environmental initiatives/projectsunder taken over the years in this sector and other substantial international secondarysources.

In this regard, we thank Pakistan Pharmaceutical Manufacturers Association (PPMA) andPharmaceutical industries for extending their support in all aspects of the study.

November, 2001


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Cleaner Production Program (CPP) vii

Page #

Executive Summary

Environmental degradation is an escalating problem owing to the continual expansion of

industrial production and high-levels of consumption. A renewed dedication to a provenstrategy to resolve this problem is needed.

The progressive industries of Pakistan have been taking individual steps to solve theirenvironmental problems under the proven Cleaner Production (CP) regime. Manyenvironmental projects have also addressed the issue and contributed towards theimprovement of environmental condition of local industries.

Cleaner Production Program (CPP) is an initiative that is focused on the consolidation ofenvironmental and CP related work done in the different major industrial sectors ofPakistan. The main objective of CPP is to continue the dissemination of cleaner productionsolutions, and enabling the industrial units at the sector level to implement the same in acost effective manner.

Free technical assistance is available under CPP to the selected industrial units against acommitment of sharing their knowledge and experience of the implementation of CPtechnologies with the other units of the same sector.

This report encompasses the nature and extent of environmental and public health problemsassociated with the Pharmaceutical sector and develop solutions in terms of cleanerproduction options and end-of-pipe treatment.

Pharmaceutical sector can be classified as one of the most organized sector with respect to

its institutional arrangements. About 200, both local and multinational industries areoperating in this sector in which the market sales of the leading multinational companiesare 50% . Most of the pharmaceutical industries are located in Sindh and Punjab.

The production of pharmaceutical products can be broken down into three main stages: 1)Research & development; 2) Conversion of organic & natural substances into bulkpharmaceutical substances or ingredients through fermentation, extraction and/or chemicalsynthesis; and 3) Formulation of the final pharmaceutical product. In Pakistan, only theformulation of pharmaceutical products is carried out and wide variety of chemical andpharmaceutical products are produced which includes anesthetics, disinfectants, watersoluble salt, muscle relaxants, anti clotting agents, analgesic, anti hypertensives, antibiotics,diuretics, anti-infective, cardiovascular, central nervous system and vitamin in the form of

capsules, tablets, ampoules, syrups, creams, etc.

Active raw materials as well as excipients like sugar, lactose etc. are used to manufacturedifferent pharmaceutical products. Besides the major raw materials, solvents such asMethylene Chloride, Di-chloro Ethane, Ethyl Acetate and Methanol are mostly used. Mostof the requirements of raw materials are met through import.

Most consumed utilities in pharmaceutical industry are electricity, water, diesel and natural gas.Generally water is required in most of the processes. Beside this it is also consumed in


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Cleaner Production Program (CPP) viii

Page #Executive Summary Pharmaceutical Sector Report

general office use, cleaning, rinsing, washing, showering, etc. Electricity consumptiondepends on the size of the unit and the degree of dependence on electric appliances. Naturalgas and diesel are mostly employed as fuel for heating purpose such as for water heating

systems, incinerator, generator, etc. Air-handling, Generator, Boilers, Water TreatmentSystemare some of the commonly used ancillaries in Pharmaceutical sector.

In Pakistan no synthesis process is done, only for mulation, filling and packaging process iscarried out in local and multinational industries. Therefore, environmental problem is not asignificant issue in the sector. Being an organized sector many of the pharmaceuticalindustries have already taken some CP initiatives. This includes proper air handling system,use of PPE, and installations of wastewater treatment systems.

Wastewater Pollution is the main issue of this sector. In pharmaceutical industrieswastewater is mainly generated through the washing activities of the equipment. Solidwaste usually comprises of expired or rejected medicines, spent solvents, packaging

material and damaged bottles. The air emission problem, mainly from generator and boilersis not significant as compared to the wastewater and solid waste.

Level of wastewater pollution varies from industry to industry depending on the type ofprocess and the size of the industry. The main pollutants in effluent are organic chemicals(responsible for BOD & COD), Grease & Oil, sulfate, Ammonia Sulfide, Phenols, TSS,TDS, etc. Ranges of BOD & COD values of wastewater are higher than the limits definedby NEQS in all industries. While in some industries the concentration of oil&grease,sulphide and TSS are also on the higher side

Air emissions are mainly from exhaust of stacks of power generator, boilers andincinerators. Emissions from these stacks mainly consist of particulate matter, NOx, SOx,

CO and CO2. These emissions are due to fuel combustion. Emissions other than stacks areVOC from printing machine, tablet manufacturing area etc.

Solid wastes are generated through different production activities. These includes expiredor rejected medicines or capsules, empty drums, glass bottles, spillages and filter & dustfrom bag filters.

The report also includes recommendations, which are focused on the above mentionedproblems of the sector. Some of the major recommendations include reduction ofwastewater from washing activities, which in turn will reduce the cost and size ofwastewater treatment plant. Regarding the EOP, on the basis of the data available, it isinferred that for combined effluent (process + domestic), biological treatment withactivated sludge system and sequencing batch reactor will be suitable before final disposalso as to comply with NEQS levels.

Extended Aeration Activated Sludge (EAAS) process and Sequencing Batch Reactor (SBR)process, both of which are modified forms of conventional activated sludge process, can beused as treatment systems, for pharmaceutical wastewater.


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Cleaner Production Program (CPP) ix

In activated sludge process, the wastewater treatment is carried out by forced supply ofoxygen or air to the wastewater and maintaining a contact, in suspension form, betweenmicroorganisms (activated sludge) and the incoming wastewater.

For the air handling system it is suggested that a procedure for its operation andmaintenance should be prepared. An air handling system refers to a system designed fordirecting air in a

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Cleaner Production Program (CPP)

Executive Summary Pharmaceutical Sector Report

positive and controlled manner through specific enclosures by means of air-handling plant,ducts, air distributing devices and automatic controls. Similarly fume hood is recommendedin main dust generating areas which include packaging, dispensing and mixing area.

Some of the major recommendations with respect to solid waste include reduction of wasteand disposal of waste under proper and safe conditions. It is suggested to set up and carryout a solid waste segregation program. The program shall also include collection anddocumentation of data on generation rates, collection/handling practices, storage anddisposal activities, for different types of wastes. This data would be helpful in properplanning of the waste disposal operations. Hazardous and non hazardous waste should bestored separately to avoid contact between each other. Waste segregation should take placeat the source of waste. All the contaminated solid waste and chemicals should besegregated from other wastes and stored under controlled conditions.

Incineration is at present considered to be a suitable technology for the disposal of wastechemicals and contaminated solid waste of pharmaceutical industry. It is the controlledthermal oxidation and decomposition of organic matter, at very high temperatures. Asprovision of a proper in-house incineration facility would not be economically feasible formost of the units, due to the kind of contaminated waste loads encountered and the highcapital cost of duly equipped incinerators. Therefore, there is need of installing a properlyequipped incineration facility, jointly and collectively by a group of pharmaceuticalmanufacturing units through PPMA.

It is recommended that the workers working in high noise areas must wear ear protectiongadgets and signs for wearing ear protection gadgets must be put in the area.

Technical details and cost estimates of recommended measures are included in the report to

facilitate the management in taking decisions for the implementations.


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Cleaner Production Program (CPP) 1

Page # viii

1Introduction

1.1 Background

Environmental degradation is an escalating problem owing to the continualexpansion of industrial production and high-levels of consumption. A reneweddedication to a proven strategy to resolve this problem is needed. CleanerProduction is one such strategy which can address this problem. It is a preventiveenvironmental management strategy, which promotes eliminating waste before it iscreated to systematically reduce overall pollution generation, and improve

efficiencies of resource use. The definition of Cleaner Production adopted by UNEPis as follows;

Cleaner Production is the continuous application of an integrated preventiveenvironmental strategy to processes, products, and services to increaseoverall efficiency, and reduce risks to humans and the environment. CleanerProduction can be applied to the processes used in any industry, to productsthemselves and to various services provided in society.

The progressive industries of Pakistan have been taking individual steps to solvetheir environmental problems under the proven Cleaner Production (CP) regime.Many environmental projects have also addressed the issue and contributed towards

the improvement of environmental condition of local industries.

Cleaner Production Program (CPP) is an initiative that is focused on theconsolidation of environmental and CP related work done in the different majorindustrial sectors of Pakistan.

The main objective of CPP is to continue the dissemination of cleaner productionsolutions, and enabling the industrial units at the sector level to implement the samein a cost effective manner.

The CPP team will be working very closely with the progressive industrial sectors ofPakistan to conclude the cleaner production research for reducing the pollution

loads.

The knowledge and experience premises of the CPP are precisely based on theprojects already implemented or projects under implementation for differentindustrial sectors of Pakistan. Predominantly the project will use the experience andknowledge of leather, textile, sugar, paper, and fertilizer sectors environmentalprojects.

Presently, CPP is working with various industrial units of Pakistan to implement


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Introduction Pharmaceutical Sector Report


cleaner production technologies as well as end-of-pipe treatment. The time framefor delivery of the project is two years.

Page #

Free technical assistance is available under CPP to the selected industrial units

against a commitment of sharing their knowledge and experience of theimplementation of CP technologies with the other units of the same sector.Assistance to the selected industrial units is provided for CP projects which are:

Critical for the sector, for environmental compliance.

Relevant and applicable to the majority of the industries in the local sector.

Technically and financially feasible.

Doable by December 2003.

Industrial units will be required to provide the resources for the implementation ofprojects along with the organization of awareness raising events, in kind, against theprovision of technical assistance by the CPP technologists.

The expected results, as output of CPP, would support industries to comply withNational Environmental Quality Standards (NEQS) and ISO 14000.

In order to ensure the sustainability of CP solutions at the sector level CPP will also

prepare guidelines for the development of sector level cleaner production projects.

1.2Overview of the Pharmaceutical Sector Environmental Report

This report for the Pharmaceutical sector is prepared on the basis of informationcollected from:

Various pharmaceutical units,

Different environmental and CP initiatives/projects undertaken over the years inthe sector, and

Substantial international secondary sources including internet.

This report encompasses the nature and extent of environmental and public healthproblems associated with the pharmaceutical sector and develop solutions in termsof cleaner production options and end-of-pipe treatment. The manufacturing processis described briefly in order to better understand the problem. This is followed by adetailed analysis of the environmental issues in terms of wastewater pollution,

process solid waste, air emissions and noise and their impacts on human beings andecology. Finally, CP solutions are described to mitigate the adverse impactsassociated with the above problems.

The findings are generalized to ensure confidentiality of unit specific information.Maximum care has been taken while generalizing the information, however,variation from one unit to another may be expected due to specific processconditions.


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1.3 Pharmaceutical Sector of Pakistan

The production of pharmaceutical products can be broken down into three mainstages: 1) Research & development; 2) Conversion of organic & natural substancesinto bulk pharmaceutical substances or ingredients through fermentation, extractionand/or chemical synthesis; and 3) Formulation of the final pharmaceutical product.In

Page #


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Pakistan, only the formulation of pharmaceutical products is carried out and widevariety of chemical and pharmaceutical products are produced which includesanesthetics, disinfectants, water soluble salt, muscle relaxants, anti clotting agents,analgesic, anti hypertensives, antibiotics, diuretics, anti-infective, cardiovascular,central nervous system and vitamin in the form of capsules, tablets, ampoules,

syrups, creams, etc.

About 200, both local and multinational industries are operating in this sector.Pharmaceutical sector can be classified as one of the most organized sector withrespect to its institutional arrangements. Annual sales of the top ten products inPakistan are given as Table 1.2 .

Most of the pharmaceutical industries are located in Sindh and Punjab. The provincewise distribution of pharmaceutical industry is shown in the following Table 1.1,whereas major market sales of the leading multinational companies are shown inTable 1.3.

Table 1.1

Province wise distribution of Pharmaceutical Industries

Province Share (No.)

Punjab 85

Sindh 85

NWFP 6

Pakistan Pharmaceutical Manufacturing Association (PPMA) represents most ofthese pharmaceutical companies with 176 members in their association. PPMA also

has an Environmental Committee to look after the sectoral issues related toenvironment.

Table 1.2

Annual Sales of Top Ten Products Rs. m

From January 2001 to December 2001

Products Company Sales

Augmentin SKB 767

Ponstan P.Davis 596

Amoxi SKB 586Velosef BMS 503

Flagyl RPR 396

Septan Wellcome 376

Ampiclox SKB 370

Neurobion M.Marker 326

Brufen Knoll 314

Erythrocyin Abbot 303


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Cleaner Production Program (CPP) Page # 5

Source: IMS

12 Mths data To Dec. 01

Page #

Table 1.3

Sales of Leading Companies

Total Market

RANKING SALES GTH OVER

PERIOD OF

JAN 01 TO

DEC 01

SHARE

%

EVO

- 43,601 7.10 100 100.0

GLAXO SMITHKLINEBEECHAM

GLAXOWELLCOMESMITH KLINE & FRENCH

11

46

21

5,8392,252

1,6361,279

672

9.15.80

16.306.209.40

10299

10999

102

13.45.2

3.82.91.5

ABBOT + KNOLL 2 2,860 2.90 96 6.6

AVENTIS

HOECHSTRHONE POULENC RORER

3

312

2,694

1,723971

19.70

13.5032.50

112

106124

6.2

4.02.2

NOVARTISNOVARTIS PH.SPECIA

NOVARTIS CONS.HEALBIOCHEMIE/SERVIPH (Ciba

Geigy)

49

1934

2,1241,091

695338

8.8011.70

4.908.00

102104

98101

4.92.5

1.60.8

PFIZER INC PARKEDAVISPFIZER

51018

1,731

1,033

699

5.00

9.30

(0.80)

98

102

93

4.0

2.4

1.6

MERCK MARKET +BOERI-I 6 1,521 5.90 99 3.5

WYETH PAKISTAN LTD 7 1,246 (8.30) 86 2.9

BRISTOL-MAYER SQUIBB

BRISTOL-MAYER SQUIBBUPSA

8

8

-

1,1011,098

3

1.90

3.30

(81.50)

959617

2.5

2.50.0

MSD 9 1,031 9.40 102 2.4

PHARMACIA & UPJOHN 10 937 (1.60) 92 2.2

ROCHE 11 768 (3.30) 90 1.8

Source: IMS


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12 Mths data To Dec01

Page #

2Production Process

This chapter contains a description of the typical production process for pharmaceuticalproducts. As already mentioned, pharmaceutical industry is not involved insynthesis and manufacturing of basic pharmaceutical ingredients, but only carriesout formulation, filling and packaging of the pharmaceutical products.

2.1 Raw Materials and Products

2.1.1 Products

Pharmaceutical industries in Pakistan formulate, fill and pack a variety of pharmaceuticalproducts, with different trade names, in the following different forms:

a. Tabletsb. Capsulesc. Syrupsd. Oral Powders for Suspensionse. Creams, Ointments and Lotionsf. Injectibles and Ampoules

2.1.2Raw Materials

Raw materials for medicines include active pharmaceutical ingredients, excipients (likesugar and lactose) and solvents (such as methylene chloride, dichloro ethane, ethylacetate and methanol). Most of the requirements of raw materials are met throughimport.

Basic raw material used in the manufacturing of empty capsules is pharmaceutical gradegelatin. Gelatin is a mixture of water-soluble proteins derived primarily fromcollagen, which is a naturally occurring protein. Other major materials used in the


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capsule manufacturing are dyes, dye -aids, preservatives and glycerin.

Variety of packaging materials like glass bottles, blisters, plastic caps, aluminum seals,polythene/paper bags, cartons, carton partitions, labels and shrink wrappers are alsoused by pharmaceutical industries.

2.2 Main Production Facilities

2.2.1 Storage Facilities

Generally raw materials, finished products, packaging materials and expired or rejectedgoods are stored in separate storage areas or separate compartments within a


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Production Process Pharmaceutical Sector Report


combined warehouse. Temperature sensitive raw materials are stored in a separatecold storage room, maintained at the desirable temperature, commonly, in the rangeof 0-8 0C. Generally solvents are store separately.

Raw materials are, mostly, kept in quarantine area after their arrival at the plant, till theirquality is tested and checked by the quality control laboratory. After the testing in

QC laboratory, approved and rejected materials are transferred and stored inseparate sections.

Some plants have installed air curtain systems at the entrances of the storage areas torestrict the entry of insects and dust. The system automatically works when the dooropens or when the material enters the warehouse. In addition there are insecticutorsmeant for killing the insects in the warehouse and production facility.

2.2.2 Manufacturing Facilities

Generally separate manufacturing areas are provided in most of the pharmaceutical plantsfor different dosage forms. In some units, production of more sensitive medicines,like antibiotics, is carried out in an exclusive manufacturing area, separated from theother manufacturing areas and provided with higher level of hygiene control andbiological safety.

Major equipment used for production of different pharmaceutical products include:

i.Mixing & Blending Vesselsii. Granulating machinesiii. Drying Chambers iv.Autoclaves and Ovens

v. Tablets Compression

Machines vi. Tablets CoatingMachines vii.Capsule ManufacturingMachines viii.EncapsulationMachinesix. A variety of purpose-built automatic or semiautomatic filling machines for

liquids in bottles, liquids in ampoules vials, powders in bottles and creams &ointments in collapsible tubes

x. A variety of purpose-built automatic Printing Machines

2.2.3 Over Printing Area

Printing machines, located in the printing area, are used for printing prices, batch number,and manufacturing and expiry dates, on the packaging materials and ampoules andvials.

In capsule manufacturing units, purpose-built printing machines are used forprinting labels, on the capsule bodies.


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2.2.4 Packaging Area

Medicines in bulk forms, after final approval from Quality Control (QC) Department, aresent to the packaging area for the desired packing, on the purpose-built packagingmachines. Medicines are filled into the primary containers. The machines which are

include:

Blister machine

Strip sealing machine

Liquid filling machine

Ointment/cream filling machine

2.3 Allied Facilities

2.3.1 Quality Control (QC/QA) Laboratory

Most of the plants maintain their own laboratories to provide for the quality control andassurance of the raw materials, packaging materials and finished products.

2.3.2 Ventilation Systems

Most of the plants have built-in forced ventilation systems, with or without airconditioning,in main process areas. The purpose of these systems is to maintain the quality of theworking atmosphere by taking away the chemical fumes and vapors, released fromprocesses to the occupational atmosphere and by supplying the fresh air to theprocess areas. Generally, the ventilation systems are provided with dust filters.

2.3.3 Chillers and Cooling Towers

Chillers and cooling towers are provided, where centralized air conditioning systems areinstalled. Cooling towers are used for the cooling of hot water generated fromchillers.

2.3.4 Fire Detection and Fighting Systems

Some of the units have installed fire detection and alarm systems. Fire fighting facilitiesrange, from plant to plant, from provision of manual fire extinguishers (carbondioxide and/or foam) to water-based fire hydrant and/or automatic sprinklersystems.

2.3.5 Boilers

Boilers are used to produce steam, which is employed for heating in the followingequipment:

a. Autoclave


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b. Tablet coating machines

c. Distillation column for production of distilled waterd. Centralized air-conditioning and dehumidification systemse. Jacketed process vessels for heating of contents

Natural gas or furnace oil is used as fuel for boilers.

2.3.6 Water Softening Units

Some of the plants soften the available water for boiler feeding purposes. Generally, cationexchange units are used, for this purpose. Water softening media needs to beregenerated, periodically at an average interval of 24-48 hours, by back washingwith high-strength sodium chloride solution.

2.3.7 Water De-ionizing Units

Process water in most cases needs to be of very low dissolved solids. The de-ionized water

is therefore produced by reverse osmosis process.

2.3.8 Water Distillation Unit

Distilled water is used in injectibles and in a variety of other medicines. Washing ofampoules is also sometimes carried out with distilled water. Distillation process isapplied to produce such water.

2.3.9 Generators

In most of the plants, electric generators are provided as standby facility, in event of mainpower failure. Generally these generators are diesel based.

2.3.10 Hydraulic Press

Some plants have hydraulic presses, for damaging the empty raw materials drums, prior totheir dispatch to the contractor, for recycling purposes. The purpose of this activityis to prevent the possible direct reuse of these contaminated drums, by somedownstream user.

2.3.11 Shredder

On-line process rejected glass bottles are mostly contaminated and therefore shall not be

reused directly. Some plants have installed shredders to break the rejected bottles,prior to their dispatch to the contractor for recycling or disposal purposes. Thisprocess prevents the possible direct use of these contaminated bottles.

2.3.12 Incinerator


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Few plants have installed their own incineration facilities for the safe disposal of theirhazardous solid and liquid wastes. Post-incineration residual ash is immobilized byfixation in cement concrete blocks.

2.4 Typical Production Processes

2.4.1 Dispensing

Raw materials are sent from storage areas to the dispensing area, where they are weighed,prior to their dispatch to the manufacturing areas. Dispensing of steroids isaccomplished after mixing with a solvent in a special totally enclosed systemequipped with HEPA filters.

2.4.2 Tablets Manufacturing

The manufacturing of tablets involves homogeneous mixing of input ingredients, such thatwhen compressed into tablets, each tablet should contain equal amount of each raw

material. The tablet manufacturing process involves the following steps: Sieving

Initial blending and Granulation

Drying and Milling

Final Blending

Compression

Coating and drying

Packaging

A brief description of the above processes follows:

a) Sieving:The raw materials are first sieved to remove the oversize particles andthen shifted to the blending vessel.

b) Initial Blending and Granulation:After sieving, materials including activeingredients and excipients are first mixed in dry form. Then the liquid mediums,like water and alcohol are added to the dry mixture in specified proportions, forthe formation of granules.

c) Drying and M ill ing:The granules are dried in the drying chamber to specifiedmoisture content limits, at the required temperatures for a specific time period.

The dried granules are then transferred to a milling machine, for grinding.

Uniform size particles are obtained with the help of a screen.

d) Fi nal Bl ending:The final mixing is carried out in a blender, with the addition oflubricants, in specified proportions. Commonly used lubricants are magnesiumstearate and stearic acid.

e) Compression :The bulk materials (granules) are fed to the tablet compressionmachines, which compresses them to the tablets of required shape and size.


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The compression machines are equipped with dust collectors to collect dust generatedduring compression, de-dusters to remove excessive dust from the tablets.


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After the completion of a batch, the compression machines are cleaned with kerosene oil.Then the machines are left overnight for the evaporation of kerosene oil.

f) Coating and Drying:Some of the tablets require coating. The coating solution isprepared by mixing the coating materials and water, in a vessel having anagitator for uniform mixing. The tablets are transferred to the coating pans,

which are equipped with spray systems to spray the coating solution on thetablets at specified temperature. When desired weight gain is obtained theprocess is stopped. The coated tablets are then dried for few minutes. Finally thelubrication of the granules has been done by mixing suitable lubricants.

g) Packaging :After coating, the tablets are ready for packing and are transferredto the packing section.

2.4.3 Encapsulation

Encapsulation is the process in which medicine is filled in the preformed capsules, on

encapsulation machines. Ingredients pass through steps of dispensing, sieving, andblending in the same way as in the tablets manufacturing, prior to being fed to theencapsulation machine.

2.4.4 Syrups Manufacturing

Preservatives are dissolved in de-ionized water in a jacketed process vessel at temperaturesof the order of 90 0C. The solution is stirred continuously and then cooled to atemperature of about 30 0C. After cooling, the active ingredients are added andstirring is restarted. Flavors are added during the process of mixing. The viscosity ofthe syrup is maintained by the addition of de-ionized water. After specified periodof mixing, syrup is taken out of vessel, filtered and stored in large storage tank,

before filling into the bottles and packing.

2.4.5 Manufacturing of Oral Powders for Suspensions

Duly formulated, mixed and homogenized powders are brought to the powder fillingmachines, where they are automatically filled in the bottles, in required quantities.Finally, sealing of the bottles is done. The bottles are labeled and packed beforetheir dispatch to the finished goods store.

2.4.6 Creams, Ointments and Lotions Manufacturing

Pharmaceutical industry is producing oil-bases and water-based creams, ointments andlotions. The excipients are mixed in the jacketed process vessels, equipped withstirrers and heating arrangements. During mixing the active ingredients are added tothe mixture. The prepared mixture is then stored in containers.

The mixture is fed to the purpose-built automatic filling machines, which are different fordifferent type of containers. The mixture is automatically filled, in required


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quantities, into collapsible aluminum tubes or bottles, as the case may be. Generally,ointments are filled in collapsible aluminum tubes, while lotions are filled in bottles.

2.4.7Injectibles Manufacturing

Ampoules and vials are first washed with de-ionized water.

a. Sterilization of Primary containers (Ampoules/vials):The primary conatiners arewashed with de-ionized and/or distilled water and then sterilized in an electricallyheated oven at about 250 0C. In some cases siliconaiztion to avoid sticking of materialsis also done.

b. Autocalving: all the dresses, equipment parts, gloves, glass containers etc are sterilizedby autoclaving.

c. Mixing and Fi ltration:Sterile liquid mixture is prepared by mixing active ingredientsand excipients in the specified ratio . The liquid mixture is then filtered under sterile

conditions. The distilled water is used for the washing of equipment, before starting themixing and filtration processes. The filtration assembly is also sterilized prior to theprocess of filtration.

c. Fil li ng and Sealing: The ampoules/vials are filled with the liquid mixture and thensealed, on the automatic filling and sealing machine.

d. Optical Checking:The filled ampoules/vials are subjected to visual inspection, underspecial light arrangement, to detect the presence of any particulate matter. The whiteparticle are optically checked against black background and black against whitebackground.

e. Printi ng and Packaging:After checking ampoules/vials are sent for printing, on aprinting machine. The final packing is done in packaging area. At the end the packedproducts are kept in big cartons and sent to warehouse for dispatch.

2.4.8 Capsule Manufacturing Process

This section presents typical process for the production of two-piece, hard gelatincapsules.

The basic process in capsule manufacturing is the preparation of gelatin solution. Solutionis processed in jacketed stainless steel melters equipped with stirrer. For transparentcapsules, solution comprises of gelatin, water and some chemicals, whereas for theopaque capsules, titanium dioxide is added in the same solution as prepared fortransparent capsules.

Manufacturing of capsules is done in an electrically operated machine equipped with allnecessary auxiliaries. The formation of capsule shape utilizes a precisionmachinedset of moulds, to which the liquid gelatin adheres, forming both the cap and bodysections. As the gelatin dries on pin, it hardens to form the capsule that is later


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removed from pin. Capsule shells are then subjected to cutting operation in amachine

in order to obtain the required size. From here significant amount of cuttings ofcapsules are generated which are collected by vacuum in plastic bags.

In Capsule Printing Machines, a conveyer belt carries capsules to the printing roller.

Capsules are printed with words, logos and symbols that provide the desiredidentification of company and product. Printed capsules are shifted to the capsulesorting area, where they are manually sorted. Defective and approved capsules areseparated.

After sorting, the approved capsules are released for packaging. Capsules are packed eitherin aluminum foil bags or in heavy-duty Kraft paper bags as per the requirement ofthe customers.

2.5 Utilities

The main utilities in the pharmaceutical sector are water, electricity and fuels.

2.5.1 Water

Water is mainly consumed in the following activities:

i. Process

ii. Washing of equipment iii. Washingof bottles and ampoules iv. Generalwashing of building areas v. Productionof steam in boilers vi. Make-up waterfor cooling towers

vii. Cooling medium in chillers for air-conditioning system viii.Qualitycontrol laboratory

ix. Miscellaneous office uses

Process water is de -ionized before use. De-ionized water is used for the followingpurposes:

i. Washing of bottles and ampoules ii.Creams and ointment manufacturing iii.Quality control laboratory

iv. Production of distilled water

Distilled water is used for injections and a variety of other medicines.

Specific total and process water consumptions are estimated as 140-180 and 100-150 liters per kg of raw ingredients, respectively. The process water does notinclude the sanitary water originating, being used for office use and general floorwashings.


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2.5.2 Electricity

The electricity is used for the following purposes, in the pharmaceutical plants:

a. Process and ancillary equipmentb. Lighting, air conditioning and forced ventilation

c. Pumps and compressors

Specific electricity consumption is estimated as 10-20 kWh per kg of raw ingredients.

2.5.3 Fuels

The natural gas is mainly used in boilers and general office use. Diesel is the most commonfuel for standby generators and incinerators.


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3Environmental Issues and Impacts

Key environmental issues, associated with the pharmaceutical industry, are asfollows:

Wastewater Pollution

Air Emissions

Process Solid Waste

Noise Pollution

This chapter presents the key environmental issues of the pharmaceutical sector and their

environmental impacts.

3.1 Wastewater Pollution

Wastewater pollution is the main environmental issue of the pharmaceutical sector. Thoughthe wastewater discharged is small in volume; but it is highly polluted, because ofpresence of substantial amounts of organic pollutants.

3.1.1 General

a. Biochemical Oxygen Demand (BOD): Biochemical oxygen demand (BOD), of

wastewater, measured in mg/l, is the amount of oxygen, required by themicroorganisms, for biochemical oxidation, of the organic matter. It is the most widelyused measure of the organic pollution of the wastewater. Commonly used parameter isBOD5 that is BOD exerted in 5 days, at a temperature of 20

0C.

b. Chemical Oxygen Demand (COD):Chemical oxygen demand (COD), ofwastewater, measured in mg/l, is the amount of oxygen, required, for thechemical oxidation, of the organic matter. COD/BOD Ratio reflects thebiodegradability potential of the wastewater. Generally, its value is higher forthe industrial wastes than for the domestic waste.

3.1.2 Wastewater Sources and Quality

Table 3.1 presents summary of the wastewater generation sources and associatedqualitative characteristics, from a typical pharmaceutical plant. The productionprocesses, in general, are ba tch type and the consequent discharges are periodic innature.


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Environmental Issues and Impacts Pharmaceutical Sector Report



Table 3.1

Typical Wastewater Generation Sources and Qualitative

Characteristics Pharmaceutical Plant

Wastewater Characteristics

Washing of Process Equipment and Vessels BOD, COD, SS, DS

Washing of Ampoules Clean Stream

Cleaning and Washing of Floors BOD, COD, SS, DS

Laboratory Wastewaters BOD, COD, SS, DS

Periodic Discharge of Boiler Blow-down Water DS

Steam Condensate Hot Clean Stream

Periodic Discharge of Cooling Tower Blow-down Water DS

Backwash Water from Water Softeners DS

Office Use & Miscellaneous BOD, COD, SS

Source: ETPI Survey

A brief description of the wastewater generation mechanisms follows:

a. Washing of Process Equipment and Vessels:This is the major source of pollutedwastewater from pharmaceutical plants.

In some units, the portable and mobile equipments or parts of the equipments are washed

in a separate washing areas, while the fixed equipment is washed at its place.

In general, the equipment are first washed with tap water and then with hot water to ensureits complete decontamination. Detergents are used as cleaning agents. Finally theequipment are dried by blowing compressed air. The autoclaves and tabletcoating machines are generally washed with caustic solution after the completionof batch.

b. Washing of Ampoules:Glass ampoules for injections are generally first washed withtap water, then with de -ionized water and final washing is done with distilled water.

c. Cleaning and Washing of F loors:The floors of process area are generally first cleaned

by vacuum cleaners to collect the dry materials and then mopped in case of spills.Occasionally the floors are washed with water. The floor washing wastewater containstraces of the spilled chemicals. Also the wastewater, generated from the washing ofbrooms, contains spilled materials.

d. Laboratory:The wastewater generated from the laboratory is mainly due to the washingactivities of laboratory utensils and accessories, which are contaminated with solvents,laboratory reagents and pharmaceutical chemicals.


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e. Boiler Blow-down:In general, total dissolved solids (TDS) are not allowed to exceed5000 mg/l in the boiler water. Higher TDS, due to their baking potential,

reduce the heat transfer efficiencies of the boiler. In order to control TDS in theboiler contents, a part of the boiler water is discharged, periodically. Theoperation is called blow-down. The blow-down water is high in TDS and alsocontains residual chemicals used for boiler water conditioning. Temperature of

blow down water is as high as 1000

C.

f. Steam Condensate:Steam is used for autoclaves, tablet coating machines, distillationunits, centralized air-conditioning and dehumidification systems and heating of jacketedprocess vessels. Steam after transferring heat becomes condensate. In cases, where thereis no arrangement for collection and reuse of steam condensate, it is discharged as awastewater.

g. Cooling Tower Blow down:Cooling towers are provided, where centralized airconditioning systems are installed. To prevent the corrosion and scaling problem in thecooling water system, intermittent blow down is usually carried out. To makeup thisloss, the level in the cooling tower is maintained by makeup water. This wastewater is

high in TDS and also contains residual chemicals used for cooling water conditioning.

h. Water Softener :Generally cation-exchange type softeners are being used by the localindustry for production of soft water, for boiler feeding. Water softening media needs tobe regenerated, periodically at an average interval of 24-48 hours, by back washing withhigh-strength sodium chloride solution. The wastewater generated in this process is veryhigh in TDS and salt contents.

3.1.3 Wastewater Quantities

Unit total wastewater quantity including the sanitary wastewater originating from office

use, floor washings and general cleaning operations is estimated as follows:

Medicine formulation 120-160 liters/Kg of raw ingredients

Since a significant part of the wastewater results from periodic discharges from batchprocesses, with varying discharge intervals, the wastewater flow rates would show arelatively higher level of daily and seasonal fluctuations.

3.1.4 Wastewater Characteristics

a. Variation in Characteristics: Following aspects are of significance, whilecharacterizing the wastewater generated by the pharmaceutical industry:

i. Temporal Vari ation in Wastewater Characteri stics:As has already beenmentioned, the polluted process wastewater, mainly, results from periodicwashing of various types of process equipment and vessels. This factor, inaddition to the flow variations, also, results into relatively higher temporal,daily as well as seasonal, fluctuations in the characteristics of thewastewater. Another factor, which may contribute to large temporalvariations, is processing of raw pharmaceutical ingredients, different typesand chemical natures, at different times.


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ii. Plant to Plant Variations: The process wastewater characteristics may showa lot of variation, from plant to plant, depending primarily upon the typesand natures of raw pharmaceutical ingredients, being processed.

The above factors make it difficult to establish a well-defined range for quality

characteristic s of pharmaceutical wastewater. The characteristics, therefore,given in the following section shall be taken as indicative only.

b. Composite Wastewater Character istics:Important pollutants encountered in thewastewater from a typical pharmaceutical plant are organic pollutants(represented by BOD and COD), suspended solids (SS) and dissolved solids(DS).

Table 3.2 presents some typical data on composite wastewater characteristics, fromdifferent pharmaceutical plants. Applicable National Environmental QualityStandards (NEQS) values are also given for the purpose of comparison.

Table 3.2

Composite Process Wastewater Characteristics

Parameters Unit Typical Concentrations NEQS

pH 6.0-7.5 6-9

BOD5 mg/l 300-400 80

COD mg/l 400-800 150

Total Suspended Solids (TSS) mg/l 200-600 200

Grease & Oil mg/l 0-13 10

Sulfide (S) mg/l 0-50 1.0

Phenols mg/l 0-1.5 0.1

Source: ETPI Survey, 2001

The above tabulated quality characteristics reveal the following:

i. The characteristics show significant variation from plant-to-plant andsampleto-sample, due to the factors already mentioned in Section (a) above.

ii. BOD and COD values of the composite wastewater exceed the NEQSvalues, whereas TSS and oil & grease may exceed in certain cases.

iii. Sulfides and phenols may also exceed NEQS. The variation could be verydrastic depending upon the process condition.

3.1.5 Impacts Associated with Wastewater

Impacts associated with the pharmaceutical plants wastewater pollutants, exceeding NEQS,are given in Table 3.3.


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Table 3.3

Environmental Impacts of Wastewater

OrganicPollutants

Depletion of the dissolved oxygen (DO) levels, of the receiving waterbody, below limits necessary to maintain aquatic life (4-5 mg/l).

Suspended

Solids

Sedimentation in the bottom of water bodies covers the natural fauna

& flora on which aquatic life depends.

Localized depletion of dissolved oxygen in the bottom layers of

waters bodies.

Reduced light penetration in natural waters and consequent reduction

in photosynthesis

Aesthetic nuisance

Oil &

Grease

Reduced re-aeration in the natural surface bodies, because of floating

oil & grease film and consequent depletion in dissolved oxygen

levels

Reduced light penetration in natural waters and consequent reduction

in photosynthesis.

Aesthetic nuisance

Sulfides Nausea and gastric pains, in human beings, by ingestion of alkali

sulfides

Fish mortality at high concentrations (10 mg/l)

Crown corrosion in public sewers by microbial production of sulfuric

acid

3.1.6 Disposal of Wastewater

In most of the units, domestic and process wastewater is collected in separatesewerage lines but before final disposal these two streams are combined and thecombined effluent is either treated in a wastewater treatment plant or disposed offdirectly to the municipal drain.

Most of the Pharmaceutical industries treat their effluent in septic tank. The septictank is viable for domestic wastewater because its function is to separate the sludge

from the effluent which undergoes partial treatment under anaerobic condition. Thebaffles in the septic tank enhance the separation of water from the sludge and theclear water is thus drained.

Some of the premier industries are endeavoring to slash the concentration ofpollutants in their wastewater through wastewater treatment plant. The treatmentsystem is based on activated sludge system. In this treatment system wastewater istreated by micro organisms (activated sludge) under aerobic condition. Main unitoperations of the system are aeration tank, degasifier, settling tank and sludge silo.


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3.2 Air Emission

3.2.1 Major Sources, Processes and Qualitative Characteristics of Air

Emissions

Broadly the air emissions can be classified as point and diffused emissions. Point emissionsare mainly from stacks and exhausts. Emissions from these sources can bequantified and easily monitored. Diffused emissions are those, which do not comethrough stacks or any exhaust and generally get directly into the occupationalatmosphere of the production areas. Table 3.4 shows the important sources,operations, mechanisms of emission and the major potential pollutants in theemissions, of pharmaceutical industry.

Table 3.4

Air Emission Sources/Operations and Major Pollutants

Source/Operation Mechanism Majo r Pollutants

Point Emissions

Exhaust of Power Generators Combustion (Diesel) PM, CO, SOx, NOx

Stacks of Boilers Combustion (Gas or

Oil)

PM, CO, SOx, NOx

Di ff used Emissions

Powdered & Granular Materials Processing Emissions of Dust PM

Printing Operations Evaporation of

solvents

VOC

Brief description of main diffused air emissions sources is as follows:

a. Powdered and Granular Mater ials Processing:Pharmaceutical formulation industrycarries out processing of a variety of pharmaceutical ingredients, which are in powderand granule form. Handling and processing of such materials may lead to emissions ofparticulate matter, into the occupational atmosphere of processing areas, in cases ofinadequate coverage of processing equipment and absence or insufficiency of local orspot ventilation systems. Quantum of particle dispersion would depend also upon theparticle size and liquid contents of the ingredients and the extent of agitation inducedduring the process. In general, the PM dispersion rate would be more in powder

formulations than in granule. Depending upon the characteristics of ingredients and theambient temperatures, some fumes may also get released, during the process.

Following are some of the specific processes and operations, of pharmaceutical plants,which may cause dispersion of particulate matter, in the processing areas.

i. Raw Ingredients Dispensing Operations: In dispensing areas, weighing of thepharmaceutical ingredients is carried out for their dispatch to the manufacturing area, in


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specified quantities. Most of the ingredients handling operations are carried outmanually. Generally open weighing machines are equipped with dust collectors.

Steroids are liquefied in the dispensing area, by addition of solvents. Steroids and solventsalso have a tendency to emit fumes and vapors.

Particles and fumes dispersion into the working air takes place, where spot ventilation is

inadequate or its operation is ineffective.

ii. Mil li ng Operation in Tablet Manufacturing:As described in Chapter 3, during tabletmanufacturing dried granules, in some cases, are ground in a mill, for obtaining uniformparticle size, prior to their compression into tablets. Milling machine is equipped with aspot dust collector.

Dust emissions to the working air are excessive, where spot ventilation is

ineffective.

iii.Feeding of Powdered and Granu lar I ngredients into Open Process Vessels: In anumber of formulation processes, powdered or granular ingredients are fed manually tothe open blending and mixing vessels. Pouring of these materials, generally, generatessignificant amount of emissions, which go into the ambient air.

iv. Encapsulation Process: In some old encapsulation machines, significant emissions ofparticulate matter take place during the capsule filling operation.

The dispersion to the working air are excessive, where spot ventilation is

ineffective.

b. Printing Operations:A number of printing operations are carried out in a typicalpharmaceutical formulation plant. Solvents, used in the printing inks, are in general

volatile and vaporize into the atmosphere. The emission quantities of vapor mainlydepend on the characteristics of the solvent and the ambient temperatures.

The common solvent used in inks for the printing of tags and labels is methyl ethyl ketone.Ethanol-based inks are commonly used for printing on the capsules, in capsulemanufacturing plants.

The smell of these vapors is generally felt in the printing areas. Effective spotventilation however results in significant reduction in the presence of vapors inthe atmosphere.

3.2.2 Existing Situation on Point Emissions

Measured concentrations of various pollutants in samples drawn from some stacks ofstandby power generators (diesel) and boilers (fuel gas or furnace oil), ofpharmaceutical industry, reveal the following:

a. Oxides of nitrogen and sulfur are within NEQS limits, in most of the cases. In somecases they exceed the NEQS values.


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b. Carbon monoxide, in most of the cases, exceed the NEQS values. In some cases, it isfound to be as high as 20 times the NEQS limiting value.

c. Relative concentrations of oxygen (O 2), carbon monoxide (CO), carbon dioxide(CO2) and hydrocarbons (HC), in the exhaust, indicate trends of incompletecombustion in some generators and boiler.

3.2.3 Existing Situation on Diffused Emissions

Most of the pharmaceutical plants have a combination of local or spot and area ventilationsystems, in the processing areas. Spot forced ventilation systems capture emissionsat the source, whereas area ventilation of the production areas is carried out, tocontinuously replace the working air, with the fresh air.

It need be realized that, because of their capability to arrest and capture the emissions atsource, local or spot ventilation systems are much more economical, practicable andviable, as compared to the general area ventilation systems, to control theoccupational air pollution. For given emission rates at the source, the concentrationof pollutants in the occupational air would primarily be inversely related to thecollection efficiency and effectiveness of the local ventilation systems. Theefficiency of the general ventilation of the area would also influence the pollutionlevel in the working air.

In practice, however, spot ventilation systems become quite ineffective, where distances ofthe suction inlet points from the sources of emissions are more than those desirable.This aspect is discussed in more details, in Chapter 4. Similarly, where ventilationsystems are provided with in-built filters, to clean the air; clogging of these filtersleads to reduction in the air flows, and consequently, to a decrease in the emissionscapturing capacity of the system. Inadequate functioning of the spot ventilation

system, results in dispersion of emissions in the working areas.

No data are available on the occupational air quality of the production areas of thepharmaceutical plants. The design as well as operational efficacy and adequacy ofthe existing local and general ventilation systems, can not be established, therefore,on a reliable basis. However, it was observed that in most of the units, the airhandling system was not working appropriately. Some of the problems aremechanical and some are in terms of organization.

3.2.4 Impacts of Air Pollutants on Environment and Human Health &Life

Impacts of common pollutants found in the air emissions from pharmaceutical plants aregiven in Table 3.5.

Table 3.5

Impacts of Air Pollutants on Environment and Human Health & Life

Particulate E Damage to plants, by choking the leaf pores and restricting

Matter photosynthesis


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Global cooling of earth by reflecting back the solar radiation

Impairment of atmospheric visibility effecting transportation safety

Deterioration of aesthetic quality of atmosphere, land and water.

Soiling of materials, physical properties and infrastructure

HL Increase in the frequency of respiratory infections such as bronchitisCarbon

Monoxide

HL Heart attack, by reducing the oxygen carrying capacity of blood

Birth defects including mental retardation and impairment of fetus

growth

Dizziness, head ache and nausea

Increase in reaction time of the drivers, a threat to the road safety

Oxides of

Sulfur

E Chlorosis and plasmolysis in plants

Damage to materials and property, by acid rains, resulting from

oxidation of sulfur dioxide to tri-oxide to sulfuric acid, after

reacting with water vapors.HL Serious lung damage, particularly in sulfate form

Respiratory diseases like Chronic bronchitis

Oxides of

Nitrogen

E Formation of photochemical oxidants

Damage to materials and property, by acid rains, resulting from

oxidation of oxides of nitrogen to nitric acid, after reacting with

water vapors.

Retardation of grow th in plants

HL Reduction in oxygen carrying capacity of blood

Impairment of olfactory sense and night visionDryness and roughness of the throat

VOC Formation of photochemical oxidants

Photo

Chemical

E Leaf discoloration and cell collapse in plant

Damage to rubber, textiles, paints and other materials

Oxidants HL Severe eye, nose and throat irritations

Severe coughing and shortness of breath

E Impacts on Environment

HL Impacts on Human Life and Health

3.3 Process Solid Waste and Waste Chemicals

There are two broad categories of process solid waste generated in a typicalpharmaceutical plant:


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a. Contaminated Process Solid Wasteb. Non-contaminated Process Solid Waste

3.3.1 Contaminated Process Solid Waste and Waste Chemicals

Table 3.6 presents contaminated process solid wastes and waste chemicals, which aregenerated in a typical pharmaceutical formulation plant. The table also providesestimated unit generation rates, for some of the wastes. The generation rates areestablished on the basis of the past available data.

Table 3.6

Contaminated Process Solid Waste and Waste Chemicals

- Pharmaceutical Formulation Industry

Waste Unit Generation Rate

(% Of Raw Ingredients)

Waste Chemicals and Solvents 0.60-1.50

Expired or Rejected Medicines 0.50-1.00

Spillage Cleaning Materials 0.05-0.15

Bag Filters & Filter Dust 0.15-0.25

Contaminated Glassware NA

Contaminated Emptied Drums NA

Source: ETPI survey

NA: Not available

A brief description of different types of waste follows.

a. Waste Chemicals and Solvents:These include all the waste chemicals, solvents andpharmaceutical ingredients, which are collected from laboratory and production areas.

b. Expir ed or Rejected Medicines:The pharmaceutical industries collect back the expiredproducts from the market. Beside this the raw materials and products, which are rejectedby the quality control departments, are separately collected.

c. Spil lage Cleaning Materi als: Accidental leakages and spillages from raw ingredientsdrums, bottles, containers, process equipment and vessels and pumps are the sources offloor contamination. A general practice is that all these spillages are either wiped with

cloth rags or cleaned with vacuum cleaner. Sawdust is also used to absorb the liquidspillages. Used cloth rags, dust from the vacuum cleaners and sawdust are collectedseparately and should be treated as contaminated waste.

d. Bag Fil ters & Fi lter Dust:In some plants, cloth filters are placed in the closed loopspot and area ventilation systems, to clean the circulating air from particulate matter.With time, as the filters get clogged with the dust, these are either cleaned or replaced.The dust and waste filters are to be treated as contaminated waste, because the dustcontains traces of the chemical ingredients.


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e. Contaminated Glassware:Following types of contaminated glassware is generated:

i. Emptied laboratory chemicals bottles ii.Damaged laboratory glassware

iii. Damaged or rejected ampoules iv. Damaged or

rejected bottles of medicines

f. Contaminated Emptied Drums: Most of the solid and liquid raw pharmaceuticalingredients are received in drums. After emptying, these drums still contain someresidual material.

3.3.2 Existing Disposal Practices of Contaminated Solid Waste

Usually, the waste chemicals and contaminated solid wastes are beingincinerated in an on-site or off-site facility. Incineration, under properlycontrolled conditions, is at present considered to be an appropriate method for

the disposal of waste chemicals and contaminated solid waste, of pharmaceuticalindustry.

Some of the progressive units have installed their own in-house incinerators. One suchincinerator is a multistage unit, comprising primary, secondary, and settlingchamber, for incineration of all types of waste chemicals and contaminated solidwaste. In primary or ignition chamber, material is charged and allowed to burn at500-8500C. The secondary chamber or after burner allows the combustion ofgases, at temperatures of about 1,000-1,200 0C. Ash and other noncombustibleresidues are collected in the settling chamber. The ash, which is obtained afterincineration, is immobilized by fixation in cement concrete blocks. Some of theunits are using of-site commercial facilities for incineration of their

contaminated waste.

The performance of the above incinerators cannot be evaluated because monitoringdata on the quantum and quality of the air emissions and residue ash contents,along with the quality and characteristics of corresponding feed materials are notavailable.

Some of the local industries are practicing open burning of their contaminatedwaste. Due to uncontrolled burning, fumes and chemicals of the pharmaceuticalchemicals, dispersed in the community air which can pose very serious healthhazards to the people.

Some of the industrial units have installed glass shredding machines, to crush thecontaminated glassware, to prevent their direct reuse. The crushed glassware isthen dispatched to the contractor for recycling or disposal purposes.

To prevent the direct reuse of contaminated empty drums, some industrial unitshave installed hydraulic presses, for damaging these. These deformed drums arethen sold to contractor for their recycling.


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3.3.3 Non-contaminated Process Solid Waste

Table 3.7 presents non-contaminated process solid wastes, which are generated in a typicalpharmaceutical formulation plant. The table also provides estimated unit generationrates, for some of the wastes. The generation rates are established on the basis of thepast available data.

Table 3.7

Non-contaminated Process Solid Waste

Pharmaceutical Formulation Industry

Waste Unit Generation Rate

(% of Raw Ingredients)

Corrugated Cartons 5.0-10.0 %

Poly bags 1.5-2.5 %

Fiber Drums NA

Wooden Pallets 4.0 %Iron Scrap 0.1 %

Non-contaminated Glassware NA

Non-contaminated aluminum cans NA

Damaged and rejected labels 4.0 %

Source: ETPI survey

NA: Not available

Most of the above-tabulated wastes are sold to the contractor for reuse or recycling by thedownstream users.

In specialized capsule manufacturing units, major process solid wastes are rejected capsuleshells and cuttings and a variety of packaging materials. Rejected capsule shells andcuttings are estimated as 10% of the product, by weight.

3.4 Noise Pollution

3.4.1 Noise Sources and Levels

Table 3.8 presents ranges of noise levels, measured at a distance of 7.5 meters from someof the process and ancillary equipment, used in the pharmaceutical plants.Permissible noise level limit, as promulgated by NEQS, is 85 dB-A.

Table 3.8

Typical Noise Levels in Pharmaceutical Industry

Equipment (Noise measured at 7.5 meters from Source) Noise Levels (dB-A)

Tablet Compression Machine 80-84


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Capsule Manufacturing Machine 87-89

Grinder 106

Glass Shredding Machine 95

Chillers for HVAC System 110

Electricity Generators (Diesel) 102-120

Source: ETPI survey

3.4.2 Potential Impacts of Noise Pollution

Noise is considered as an interference to and imposition upon comfort, health andthe quality of life. Noise may have both physiological as well as psychologicaleffects on human beings.

Physiological effects include dizziness, nausea, unusual blood pressure variation, physicalfatigue, hearing impairment and, in acute cases, permanent hearing loss. Thepsychological effects may comprise reduced mental capability and irritations.

Chronic exposure of workers to higher noise levels also impairs their efficiency andskill.


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4Recommendations

This chapter lays down general recommendations, on the following environmental issuesof pharmaceutical sector:

a. Wastewater Treatmentb. Occupational Air Quality Control

c. Contaminated Solid Waste and Waste Chemicals Managementd. Occupational Health and Safety Measures

4.1 Wastewater Treatment4.1.1 General

The following recommendations are applicable to the wastewater originating frompharmaceutical formulation plants.

It is suggested that, in general, both the wastewater from office use and the processwastewater shall be combined for the purpose of treatment.

4.1.2 Wastewater Quantities

It is suggested that prior to going for the implementation of wastewater treatment, theindustrial unit shall carry out detailed flow monitoring and characterization of thewastewater. In the absence of such data, however, the unit wastewater quantities,laid down in Section 3.1.3, may be used for establishing wastewater flows, forpreliminary analysis and design.

4.1.3 Wastewater Characteristics and Effluent Quality Standards

As already mentioned in Chapter 3, the composite wastewater characteristics may varyfrom plant-to-plant and day-to-day, depending mainly upon the type ofpharmaceutical ingredients being processed.

In Table 3.2 of Chapter 3, some typical data on composite wastewater characteristics,based on field sampling and laboratory measurement, from different pharmaceuticalplants is presented. Table 4.1 presents expected maximum-day compositewastewater characteristics of pharmaceutical formulation plants. Required degreesof treatment, to meet the National Environmental Quality Standards (NEQS), arealso established.

Table 4.1


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Recommendations Pharmaceutical Sector Report


Maximum Day Composite Wastewater Characteristics and Required

Degree of Treatment Pharmaceutical Formulation Plant

Parameter Unit Expected

Values

NEQS[1] RequiredDegree of

Treatment (%)Value of pH 6.0-7.5 6-9

Biochemical Oxygen Demand (BOD) Mg/l 300-400 80 73-80

Chemical Oxygen Demand (COD) Mg/l 400-800 150 63-80

BOD/COD Ratio 0.40-0.75

Total Suspended Solids (TSS) Mg/l 200-600 200 0-67

Sulfide (as S) Mg/l 0-50 1.0 0-98

Phenols Mg/l 0-1.5 0.1 0-93

[1] NEQS for disposal to Inland Waters

Organic pollutants, represented by BOD and COD, are the principal pollutants. BODto-COD Ratio ranges from 0.4 to 0.75, which shows that wastewater is highlybiodegradable and would respond effectively to the biological treatment.

In some plants sulfides and phenols are present in very high concentrations in thewastewater. In such cases, wastewater will also require treatment for their removal.

4.1.4 Proposed Wastewater Treatment System for Removal of OrganicPollutants

a. Proposed Treatment Process:Extended aeration activated sludge process is being

commonly employed for the treatment of combined wastewater from pharmaceuticalformulation plants. The system is contrasted from the conventional activated sludgeprocess, by relatively low food-to-microorganism ratios and longer retention periods.The sludge production is less as compared to conventional activated sludge process. Thesystem, due to longer hydraulic retention periods, can absorb pollution load fluctuationsand is relatively easy to operate and monitor, as compared to the conventional activatedsludge process.

The biological treatment is carried out by forced supply of air to the wastewater in theaeration tank, where a contact, in suspension form, is maintained betweenmicroorganisms (activated sludge) and the incoming wastewater. The aeratedeffluent is then allowed to pass though a secondary clarifier to separate the

biomass or the activated sludge. A part of the "activated sludge", removed in thesecondary clarifier, is recycled to the aeration tank to maintain optimummicroorganism concentrations. The remaining secondary sludge is removed fromthe system periodically. The waste sludge received is reasonably stabilized anddoes not generally require any further treatment, except for de -watering anddrying, for reduction in its volume. The waste sludge can be dewatered and driedon sludge drying beds or in sludge filter press. In case of sludge filter press, asludge thickener shall also be installed before the filter press.


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The sludge, in case of pharmaceutical plants, shall be treated as contaminated solid wasteand be incinerated. Excess sludge can also be directly incinerated without anydewatering; but this will incur very high operational costs. Incineration of sludgeafter dewatering and drying is suggested.

Pharmaceutical wastewater may, sometimes, contain substances, which are toxic to the

microorganisms. Presence of such substances may inhibit the microbial growth,required for the proper functioning of the activated sludge process. In such cases,toxicity of wastewater can be controlled by addition of powdered charcoal in theaeration tank. Charcoal exhibits excellent potential for adsorbing a variety oftoxic organic chemicals. Required dosages can be established by carrying outlaboratory scale studies. The charcoal particles would be removed from thewastewater in secondary clarifier, along with secondary sludge.

b. Performance of Existing Treatment Systems:Measured treatment efficiencies, of anexisting wastewater treatment plant, based on extended aeration activated sludge plant,with aeration period of about 32 hours, for a pharmaceutical formulation industry, aregiven in Table 4.2.

Table 4.2

Treatment Efficiencies Based on CompositeWastewater Characteristics Existing Extended Aeration Activated

Sludge Plant (Pharmaceutical Formulation Plant)

Parameter Unit Influent Effluent Treatment

Efficiency

(%)

NEQS[1]


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Value of pH 7.5 7.7 6-9

Biochemical Oxygen Demand (BOD) Mg/l 223 29 87 % 80

Chemical Oxygen Demand (COD) Mg/l 452 53 88 % 150

Total Suspended Solids (TSS) Mg/l 140 27 81 % 200

Anionic Detergents (as MBAS) Mg/l 4.0 2.2 45 % 20

[1] NEQS for disposal to Inland Waters

The results show that proposed process is capable of achieving a highdegree of treatment.

c. Treatment Facilities:Extended aeration activa ted sludge process in general shallcomprise the following process facilities. Buildings (if required) and external works arenot mentioned.

i. Wastewater Screening andPumping Station

ii. Aeration Tank iii. SecondaryClarifier iv. Sludge PumpingStation v. Sludge Drying Beds

or

Sludge Thickening Tank + Sludge Press Filters

d. Sulf ides Removal: In some pharmaceutical formulation plants, sulfides are present inwastewaters in concentrations, much exceeding the NEQS limits and, therefore, need tobe removed, prior to its disposal. In one example, these sulfides existed at pH of 6.2-6.8.In general, also, the pH values of the pharmaceutical wastewater are found to be in theclose-to-neutral range of 6 to 7.5.

Sulfides change their forms, in water mediums, with change in its pH value. The chemicalbalance of sulfides in wastewater is such that, at a pH value of 9, hydrogensulfide (H2S) formation takes place. The concentration of hydrogen sulfideincreases with decrease in pH and reaches to a relative concentration of 100% atpH of the order of 5. On the other side, at pH of 8, formation of alkaline andmetallic sulfides takes place, which increase with the increase in the pH value.At pH value of 7, about 50% of the sulfides exist as hydrogen sulfide.

It is expected that hydrogen sulfide present, in close-to-neutral or slightly acidicpharmaceutical wastewaters, would be stripped of and removed, consequent toforced aeration of wastewater, in activated sludge reactor. Stripping of hydrogen

sulfide, from wastewater at an instant, would lead to formation of morehydrogen sulfide, to maintain the chemical balance. Extended aeration, for aperiod of the

order of 24 hours, would result in a continuous chain reaction of formation andstripping of hydrogen sulfide. It is envisaged that in this way, required removalof the sulfides would be achieved, in extended aeration activated sludge processand in most of the cases, no separate treatment for removal of sulfides would berequired.


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e. Estimated Un it Costs of Tr eatment System:Unit capital cost of extended aerationactivated sludge treatment system, with provision of sludge drying beds, including civil,mechanical and electrical works, for a pharmaceutical formulation plant, is estimated asRupees 20,000 to 30,000 per kg/d of BOD load.

Variation in the unit capital cost of the treatment systems principally reflects the factor of

economy of scale or size of the treatment system and extent and quality of theelectro-mechanical equipment installed.

Due to the fixed cost factors, however, the capital cost of the smallest plantwould not be less than Rupees 2.00 million.

Unit annual operation and maintenance (O&M) cost (excluding the dried sludgeincineration cost) is estimated as Rupees 10 to 15 per kg of annual BOD load,with a minimum total annual O&M cost of Rupees 250,000.

4.1.5 Activated Carbon Adsorption Treatment for Removal of Phenols

In some pharmaceutical wastewaters, phenols are found to be present, in concentrationsexceeding the NEQS values and treatment would be required for their removal.

Activated carbon is very effective for removing a number of dissolved organic chemicals,by process of chemical adsorption. In this system, wastewater is filtered through anactivated carbon filter. After a period of use, depending upon the total pollution loadof dissolved organic compounds removed by the filter, the activated carbon mediagets exhausted and becomes ineffective. The spent media shall then either bereplaced with fresh activated carbon or alternatively it can be reused afterregeneration. One most commonly used method of exhausted activated carbonregeneration is its incineration at high temperatures.

In order to maximize the effectiveness of the activated carbon adsorption, it is suggestedthat, where required, this treatment shall be carried out after activated sludgeprocess.

4.2 Occupational Air Quality Control

As already described in Chapter 3, the major process related air emissions, to theoccupational air, in a typical pharmaceutical formulation plant, which can affect theoccupational air, are as follows:

a. Emissions of Particulate Matter from Processing of Powdered and GranularMaterials

i. Raw Ingredients Dispensing Operations ii.Milling Operation in Tablet Manufacturing

iii. Feeding of Powdered and Granular Ingredients into Open Process Vessels iv.Encapsulation Process

b. Emissions of Vapors from Printing Operations


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The process of controlling the occupational air quality comprises the following sequentialsteps:

a. Establishing the occupational air quality criteria, need to be maintained, for theprotection of the health and safety of the workers. Main features of the criteria are

described in Annexure I.

b. Planning, designing, installation and operation of a comprehensive system, whichensures maintenance of the occupational air quality, within the desirable limits. Such asystem would comprise the following components:

Enclosure of the emission sources, where possible

Local or spot ventilation system

General area or room ventilation system

Personal protection

c. Continuous monitoring of the occupational air and other related parameters, to checkand ascertain that the intended air quality is being achieved.

The recommendations, on the above-mentioned steps, applicable to the production areas ofpharmaceutical industry, follow:

4.2.1 Enclosure of the Emission Sources

As far as practicable, the medicines formulation and filling equipment, involvingprocessing of powdered, granular and vaporizing ingredients, should be enclosed. Ifemissions to working area can be reduced by a better enclosure, this should beintroduced first. Such enclosures also help improve the performance and

effectiveness of the spot ventilation system.

4.2.2 Criteria for Local or Spot Ventilation System

The purpose of spot or local ventilation system, in industrial production areas, is to captureand arrest the vapors, fumes and particulate matter, at the source of their emissions,before they get dispersed to the working air. Such systems are highly economical,practicable and viable, as compared to the general area ventilation, to control theoccupational air pollution. For certain emission rates at the source, the concentrationof pollutants in the occupational air would primarily be inversely related to thecollection efficiency and effectiveness of the local ventilation systems.

Following criteria and guidelines may be used by the pharmaceutical industry, forthe design of local ventilation system. Values of various parameters, as suggested infollowing paragraphs, may, however, be changed in the light of on-site observationsand experiential information.

a. General


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Local ventilation system shall mainly comprise collection hoods, airtransmission ducts, exhaust-air blowers and pre-emission or pre-circulatingair treatment system.

All the localized vapors, fumes or particulate matter emission sources, in theprocess areas, should be provided with spot ventilation.

Substantially enclosed units should also

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